Autophagy and Antigen Presentation

One-third of all eluted major histocompatibility complex (MHC) class II natural ligands are derived from endogenous cytosolic or nuclear proteins, but the underlying pathway has been difficult to pinpoint. EBNA1, the dominant CD4+ T cell antigen of the human oncogenic Epstein-Barr virus (EBV), is the sole viral antigen present in all EBV-associated malignancies. Paludan et al. describe how autophagy, a process by which the cell degrades defunct cytosolic components in times of stress, leads to MHC class II processing and presentation of endogenous EBNA1. The viral protein was imported into lysosomes by autophagy where a subset of lysosomal proteases was responsible for EBNA1 degradation. Furthermore, inhibition of autophagy decreased target recognition by EBNA1-specific CD4+ T cell clones.